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Aims: The association between a pregnant mother's vitamin D status and depressive symptoms has yielded inconsistent results. It is possible that other factors play a role in this association, as depression can have multiple causes. Recognizing the significance of the husband's participation in antenatal care, this study aimed to examine whether the husband's involvement moderates the link between the mother's vitamin D status and depressive symptoms during pregnancy., Methods: A total of 2983 Chinese married pregnant women, in their 25-35 weeks of pregnancy, completed questionnaires to assess their levels of depressive symptoms and the involvement of their husbands in their antenatal care appointments. Additionally, their serum levels of vitamin D were measured., Results: After adjusting for maternal age, parity, and socio-economic status, the husband's involvement in antenatal care moderated the association between maternal vitamin D status and depressive symptoms during pregnancy (β = 2.03, p  = 0.035). Specifically, when their husbands were not regularly present for antenatal care appointments, mothers with suboptimal vitamin D levels experienced more depressive symptoms than those with optimal levels. However, there were no noticeable differences in depressive symptoms between vitamin D groups for mothers whose husbands attended all antenatal care appointments., Conclusions: Pregnant women who have suboptimal vitamin D levels and lack support from their spouses are most vulnerable to experiencing depression. It is crucial to holistically assess the social and physiological needs of expectant mothers to reduce their risk of antenatal depression.

Norovirus is the worldwide leading cause of gastroenteric diseases. It affects mainly infants and older adults, but the findings are mainly derived from outbreak investigations rather than population-based cohorts. The U. S. Naval Medical Research Unit SOUTH (NAMRU SOUTH) developed and conducted research studies in the last 20 years focusing on the military and general populations afflicted by this pathogen. For the latter, studies included all age groups in 2 main communities in Peru, representing people from the highlands and tropical areas. The results helped elucidate the incidence of norovirus infection among different age groups as well as identifying risk factors, seasonality, and economic burden on the patient. The collected data demonstrate an increase of norovirus cases, not only in the previously reported age groups but also in adults. Consequently, this increase of norovirus cases in adults may impair the occupational productivity in civilian populations and operational readiness among service members., Competing Interests: Potential conflicts of interest. The authors do not have a commercial or other association that might pose a conflict of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2025.)

Vaccinating healthcare personnel (HCP) is a top priority for public health globally. This strategy aims not only to protect HCP but also patients, reducing transmission of infections in healthcare services. However, improving vaccine coverage in HCP is still a challenge, especially because they are a risk group for acquiring influenza. Multicomponent influenza vaccination programs targeting behavioral, organizational, and administrative barriers are critical to ensure this priority population is vaccinated. Here, we describe a healthcare worker cohort study that was implemented in Peru, a middle-income country, in 2016, prior to the coronavirus disease 2019 pandemic. This cohort, which is still ongoing, has collected valuable information on influenza vaccine effectiveness, vaccine coverage, risk factors, absenteeism, and use of personal protective equipment, as well as risk of influenza disease, among others. These data can help improve knowledge not only about influenza diseases but also regarding vaccination on this specific influenza risk group in order to improve vaccine uptake., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2025.)

Early diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) is crucial for better disease management and outcome. To ensure timely diagnosis, a multidisciplinary panel of Portuguese experts, including cardiologists, internal medicine specialists, and general practitioners, have developed a national consensus to aid physicians in enhancing the referral of patients with suspicion of ATTR-CM in Portugal. A structured approach was used to develop the consensus: (1) an online survey aimed at identifying clinical red flags, patient journeys, and diagnostic tools related to ATTR-CM; (2) a face-to-face roundtable meeting where the survey findings were discussed and a consensus was reached on referral and diagnostic algorithms for ATTR-CM in Portugal; and (3) critical review of the proposed algorithms. The referral and diagnostic algorithms for ATTR-CM in Portugal were developed considering current recommendations, but also the existence of a nationwide network of specialized cardiomyopathy clinics and national reference centers for familial amyloid polyneuropathy due to the endemic p.V50M variant. This collaborative effort aims to enhance awareness, facilitate timely referrals and improve early diagnosis, ultimately ensuring better management of ATTR-CM patients in Portugal., (Copyright © 2025 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Competing Interests: Conflict of interest Marques N: Speaker and consulting honoraria from Pfizer and Alnylam. Support for travel/accommodation for congresses from Pfizer and Alnylam. Aguiar Rosa S: Speaker and consulting honoraria from Pfizer. Consulting honoraria from Astra Zeneca. Support for travel/accommodation for congresses from Pfizer. Cordeiro F: Support for travel/accommodation for congresses from Pfizer. Menezes Fernandes R: Support for travel/accommodation for congresses from Pfizer, Alnylam and Akcea. Ferreira C: Speaker and consulting honoraria from Pfizer. Research grant from Pfizer. Support for travel/accommodation for congresses from Pfizer. Bento D: Speaker honoraria from Pfizer. Support for travel/accommodation for congresses from Pfizer and Alnylam. Brito D: Fees for consultancy, scientific lectures and/or research, from Alnylam, AstraZeneca, Bayer, BMS, NovoNordisk, and Pfizer. Cardim N: Speaker and consulting honoraria from Pfizer. Support for travel/accommodation for congresses from Pfizer. Lopes L: Speaker honoraria from Alnylam, BMS, Sanofi. Consulting fees from BMS, Novo Nordisk. Grant from BMS. Azevedo O: Speaker and consulting honoraria from Pfizer and Alnylam. Support for travel/accommodation for congresses from Pfizer, Alnylam and Astra Zeneca.

The acoustic modeling of materials is of paramount importance for the accurate prediction of untested configurations and the development of optimal manufacturing strategies. Nevertheless, this task presents significant challenges due to the complexity of the parameters governing materials, such as porous media, each of which demands distinct experimental setups and procedures, often difficult to implement. Inverse methods for parameter estimation rely on physical approximations and require experimental protocols that are highly sensitive to boundary conditions, rendering the process both expensive and time-consuming. This study investigates the efficacy of machine learning techniques, particularly artificial neural networks, in determining the parameters of the Johnson-Champoux-Allard (JCA) model for porous samples, with a specific emphasis on the mutual influence of input features on network performance. Building upon these insights, a hierarchical artificial neural network-based procedure is proposed and validated using experimental data to predict the JCA parameters with minimal error., (© 2025 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).)

Acute kidney injury (AKI) is associated with an increased risk of morbidity, mortality, and healthcare expenditure, posing a major challenge in clinical practice, and affecting about 50% of patients in the intensive care unit (ICU), particularly the elderly and those with pre-existing chronic comorbidities. In health, intra-renal blood flow is maintained and auto-regulated within a wide range of renal perfusion pressures (60-100 mmHg), mediated predominantly through changes in pre-glomerular vascular tone of the afferent arteriole in response to changes of the intratubular NaCl concentration, i.e. tubuloglomerular feedback. Several neurohormonal processes contribute to regulation of the renal microcirculation, including the sympathetic nervous system, vasodilators such as nitric oxide and prostaglandin E2, and vasoconstrictors such as endothelin, angiotensin II and adenosine. The most common risk factors for AKI include volume depletion, haemodynamic instability, inflammation, nephrotoxic exposure and mitochondrial dysfunction. Fluid management is an essential component of AKI prevention and management. While traditional approaches emphasize fluid resuscitation to ensure renal perfusion, recent evidence urges caution against excessive fluid administration, given AKI patients' susceptibility to volume overload. This review examines the main characteristics of AKI in ICU patients and provides guidance on fluid management, use of biomarkers, and pharmacological strategies., Competing Interests: Declarations. Consent for publication: Not applicable. Consent to participate: Not applicable. Ethics approval: Not applicable. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: This study aimed to define the frequency of positivity of several immunohistochemical markers in uterine tumor resembling ovarian sex cord tumor (UTROSCT)., Methods: All consecutive UTROSCT cases were retrieved from consultation files of one of the authors. Histological and immunohistochemical slides were reviewed. In addition, three electronic databases were searched from their inception to January 2024 for all studies assessing the immunophenotype of UTROSCT. Exclusion criteria were: sample size < 10 patients, overlapping patient data, reviews. Endometrial stromal tumors with sex cord-like areas (formerly called "type I UTROSCT") were excluded. Immunohistochemical markers assessed in ≥ 10 cases in at least 3 different series were included. For each marker, pooled positivity rate was calculated by using a random effect model; mean labeling index was calculated for Ki67., Results: Thirty UTROSCT cases were retrieved Six studies were included, and 30 new cases were obtained, with a total of 181 UTROSCTs. Fourteen immunohistochemical markers were assessed. Pooled positivity rates were (in descending order): CD56 = 97 %, progesterone receptor = 91 %, estrogen receptor = 85.5 %, WT1 = 84 %, wide-spectrum cytokeratins = 78.7 %, CD99 = 77 %, desmin = 74.5 %, calretinin = 70.6 %, smooth muscle actin = 56.4 %, inhibin = 44.5 %, CD10 = 41 %, caldesmon = 21.9 %, Melan-A/MART-1 = 10.4 %. Mean Ki67 labeling index was 8.7 %., Conclusions: Immunophenotypically, UTROSCT is less consistent than ovarian sex cord tumors and overlaps with other mesenchymal and epithelial tumors; an integrated clinico-pathological and immunohistochemical evaluation appears necessary for a correct diagnosis., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2025 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Chronic coronary syndromes (CCS) are the most common clinical manifestation of coronary atherosclerosis. Coronary computed tomography angiography (CCTA) is a recent innovation in non-invasive cardiac imaging. It is the only anatomical imaging method that allows direct visualization of the coronary lumen, vessel walls, and atherosclerotic plaques, offering high sensitivity and a strong negative predictive value. CCTA is particularly useful in identifying or ruling out coronary atherosclerosis in the context of CCS and serves as an excellent filter for invasive coronary angiography. Compared to other non-invasive functional imaging tests (stress echocardiography, single photon emission computed tomography, magnetic resonance imaging, positron emission tomography), CCTA provides detailed characterization of both obstructive and non-obstructive plaques, enabling accurate risk stratification and guiding therapy. Recent advances in computed tomography technology and imaging techniques further extend the use of CCTA beyond plaque and stenosis evaluation, offering also functional lesion information. This consensus document aims to detail the technical aspects of CCTA and illustrate its role in optimizing CCS diagnostic and therapeutic management, enhancing precision medicine and personalized patient care.

Purpose of Review: This review intends to systematize the diagnostic and treatment approach to cerebral venous thrombosis (CVT), highlighting key studies that have been recently published., Recent Findings: In light of the recent pandemic, new risk factors for CVT have emerged. Contrast-enhanced MRI and susceptibility-weighted imaging have been shown to offer increased sensitivity for detecting cortical vein thrombosis.Dabigatran seems to be as effective and well tolerated as warfarin for long-term anticoagulation. Partial venous recanalization often occurs in patients treated with anticoagulation only, as early as 8 days after treatment onset. For patients with CVT and impending brain herniation, two-thirds of those who undergo decompressive craniectomy survive, with one-third being functionally independent 6 months after diagnosis., Summary: CVT is an unusual type of cerebrovascular disease that mostly affects women of fertile age. Risk factors should be identified and addressed. Diagnosis relies on confirmation of venous sinus and/or vein thrombosis, usually by CT venography or MRI. Anticoagulation is the cornerstone of treatment. Despite the lack of high-quality evidence, endovascular treatment is often considered in severe cases. Special populations require tailored approaches. About 80% achieve mRS 0-1, but residual symptoms often affect quality of life and the ability to return to work., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Artificial intelligence (AI) algorithms, particularly deep learning, are automatic and sophisticated methods that recognize complex patterns in imaging data providing high qualitative assessments. Several machine-learning and deep-learning models using imaging techniques have been recently developed and validated to predict difficult airways. Despite advances in AI modeling. In this review article, we describe the advantages of using AI models. We explore how these methods could impact clinical practice. Finally, we discuss predictive modeling for difficult laryngoscopy using machine-learning and the future approach with intelligent intubation devices., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.)

Dysphagia is a leading cause of morbidity and mortality among individuals with Parkinson's disease (PD). The primary objectives of the present study were to explore patients' narrative reports focused on what information and evaluation and treatment experiences they identified as they manage dysphagia, and to identify practice patterns relevant to dysphagia management. A secondary objective was to produce an educational resource for this population that addressed their questions about dysphagia. A sample of individuals with oropharyngeal dysphagia secondary to PD (n = 25) across all regions of the United States were interviewed using open- and closed questions and a written questionnaire. Verbatim interview transcripts were interrogated using qualitative content analysis (QCA) with an inductive approach to identify themes from the participants' reported knowledge of dysphagia and experiences with swallowing evaluation and treatment. Authors developed a pamphlet addressing common questions that participants posed in the interviews and conducted a member check to revise it with their feedback. Most participants reported having been asked about their swallowing function by a healthcare professional. 60% of the sample reported having had a swallowing evaluation. Only 20% (5/25) of participants reported having completed swallowing therapy. Some participants did not know that swallowing therapy exists. Nearly all participants reported having a strong desire to know more about dysphagia and preferred a pamphlet as a resource format. Few of the study participants had received swallowing therapy, and nearly all participants were eager to learn about the nature of dysphagia, its progression, and treatment options. Given the physical, emotional, and social ramifications of living with dysphagia, access to swallowing education and treatment needs to be a stronger focus of PD management., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Immunotherapy represents an emergent and heterogeneous group of anticancer treatments harnessing the human immune-surveillance system, including immune-checkpoint inhibitor monoclonal antibodies (mAbs), Chimeric Antigen Receptor T Cells (CAR-T) therapy, cancer vaccines and lymphocyte activation gene-3 (LAG-3) therapy. While remarkably effective against several malignancies, these therapies, often in combination with other cancer treatments, have showed unforeseen toxicity, including cardiovascular complications. The occurrence of immuno-mediated adverse (irAEs) events has been progressively reported in the last 10 years. These irAEs present an extended range of severity, from self-limiting to life-threatening conditions. Although recent guidelines in CardioOncology have provided important evidence in managing cancer treatments, they often encompass general approaches. However, a specific focus is required due to the particular etiology, unique risk factors, and associated side effects of immunotherapy. This review aims to deepen the understanding of the prevalence and nature of cardiovascular issues in patients undergoing immunotherapy, offering insights into strategies for risk stratification and management., Competing Interests: Declarations. Conflict of interest: The authors have nothing to declare., (© 2024. The Author(s).)

Background: Malnutrition and muscle weakness are highly prevalent in critically admitted patients. To overcome sarcopenia and muscle weakness, physical activity and neuromuscular electric stimulation have been introduced with limited efficacy. Thus, several anabolic remedies have been introduced. An adequate increase in protein support according to indirect calorimetry and body composition and methyl hydroxybutyrate (HMB) is emerging. Therefore, we wanted to investigate the impact of HMB-enriched whey formula on the nutritional status, muscle weakness, and clinical course of critically ill patients undergoing nutritional status multimodal assessment and physical rehabilitation., Methods: We consecutively enrolled critically ill adult patients admitted to the intensive care unit (ICU) of "Santa Maria Hospital", Terni, Italy. All patients underwent preliminary anthropometric, laboratory tests, nutritional (bioimpedance vector analysis and indirect calorimetry), and ultrasound muscle assessment at admission (T0). Laboratory tests monitoring continued throughout the ICU stay. Nutritional and muscle strength assessment was taken weekly throughout the patient's ICU stay. All patients were enterally administered with a whey protein-enriched formula. Ten days after admission (during the physical rehabilitation period), patients were randomly administered a mixture of essential amino acids and methyl hydroxybutyrate (HMB)., Results: We consecutively enrolled 54 ICU patients. At the baseline, survivors (n = 46) were significantly younger than non-survivors. The latter had a worse SAPS II score, nutritional status, and risk, with no significant difference in basal metabolism. Prealbumin values significantly correlated with improved nutritional status and metabolism. Starting from 10 days upon ICU admission, the pennation angle (used as a measure of muscle strength) significantly correlated with the improvement in nutritional status. Whey proteins were well tolerated. Its administration showed a tendency to improve the pennation angle. No specific effect of the mixture containing essential amino acids and methyl hydroxybutyrate was observed. Nutritional status improvement and the rise of basal metabolism were significantly correlated with the extubation time. On the other hand, the reduction in muscle weakness was not significantly correlated with the timing of extubation., Conclusions: Whey protein formula administration can significantly improve nutritional status and basal metabolism in ICU patients. This is reflected in improved muscle strength. Whey protein administration shows a tendency toward a rise in pennation angle. A similar and non-specific trend was observed upon HMB mixture add-one. Further prospective large-scale controlled studies are needed to confirm these promising results.

Background: Prone position has been diffusely applied in mechanically ventilated COVID-19 patients. Our aim is ascertaining the association between the physiologic response and the length of the first cycle of prone position and intensive care unit (ICU) mortality., Methods: International registry including COVID-19 adult patients who underwent prone positioning. We measured the difference for arterial partial pressure of oxygen to inspired fraction of oxygen ratio (PaO2/FiO2), ventilatory ratio, and respiratory system compliance (Crs) between baseline supine position and at either the end of the first cycle of prone position (Delta-PP) or re-supination (Delta-PostPP)., Results: We enrolled 1816 patients from 53 centers. Delta-PP and Delta-PostPP for PaO2/FiO2 were both associated with ICU mortality [OR (95% CI) 0.48 (0.38, 0.59), and OR (95% CI) 0.60 (0.52, 0.68), respectively]. Ventilatory ratio had a non-linear relationship with ICU mortality for Delta-PP (p = 0.022) and Delta-PostPP (p = 0.004). Delta-PP, while not Delta-PostPP, for Crs was associated with ICU mortality [OR (95% CI) 0.80 (0.65, 0.98)]. The length of the first cycle of prone position showed an inverse relationship with ICU mortality [OR (95% CI) 0.82 (0.73, 0.91)]. At the multivariable analysis, the duration of the first cycle of prone position, Delta-PP and Delta-PostPP for PaO2/FiO2, and Delta-PostPP for ventilatory ratio were independently associated with ICU mortality., Conclusion: In COVID-19 patients with acute respiratory failure receiving invasive mechanical ventilation and prone positioning, the physiological response to prone position is associated with ICU mortality. Prolonging the duration of the first cycle of prone position is associated with improved survival., Competing Interests: Declarations. Ethics approval and consent to participate: The registry was designed following the Declaration of Helsinki and the study protocol was firstly approved by the Ethics Committee of the Saint Bortolo Hospital, Vicenza, Italy (Study ID Numbers: 22/21). Patient consent was obtained according to the national regulations of each participating Institution. In cases the patient was incompetent because of critical illness or the use of sedative or anesthetic drugs, consent could be delayed, and a provision for delayed consent was applied: as soon as competent, each patient was fully informed on what had been done, and a written permission of using data collected was obtained. The patients or their legal surrogates were informed of their right to request that the study procedures be discontinued and their right to refuse the study-related use of their medical records. Consent for publication: Not applicable. Competing interests: We declare no competing interests., (© 2025. The Author(s).)

Objective: This study assessed (1) the feasibility and usability of traumatic brain injury (TBI) assessment using the Ohio State University TBI Identification Method (OSU-TBI-ID) in a sample of English and Spanish-speaking refugees and asylum seekers (hereafter refugees), and (2) the prevalence and characteristics of TBI in this population., Setting and Participants: Refugees seeking care from Massachusetts General Hospital (MGH) Asylum Clinic, the MGH Chelsea HealthCare Center, and other asylum programs in the Greater Boston Area., Design and Main Measures: Bilingual clinical research coordinators screened 158 English and Spanish-speaking refugees using the OSU-TBI-ID. A "positive" screen for TBI was made if a participant reported loss of consciousness (LOC) or being dazed or confused following a head injury, with determinations of mild, moderate, and severe TBI based on established metrics of TBI severity using duration of LOC. We conducted descriptive statistics of the sample demographics and screening outcomes, including group comparisons between those with and without TBI and associated demographic characteristics., Results: The mean age was 36.8 years (SD: 9.1), with participants predominantly from Latin America and the Caribbean (51%), followed by Sub-Saharan Africa (35%). Less than half (43%) identified as men. The majority (59%) screened positive for having experienced at least 1 TBI in their lifetime. Among those with a TBI history, nearly three-quarters (73%) had a mild TBI, and about a third (38%) had sustained a moderate-to-severe TBI. A majority (56%) had more than 1 TBI and about 40% had sustained a childhood TBI. The most common mechanisms of injury were interpersonal assault (55%) and blunt trauma by an object (46%). There were no significant statistical differences in demographics and TBI characteristics., Conclusion: Our findings demonstrate the feasibility and usability of the OSU-TBI-ID in a sample of refugees. We call for greater and improved detection of TBI among refugees to ensure they receive the optimal care they need., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Extreme weather events due to human activities have significantly increased the frequency and severity of hydrological disasters like floods, impacting human health and healthcare systems worldwide. This study analyses the patterns of emergency service utilisation of the May 2023 flood in Romagna, Italy, and specifically investigates the differences in emergency department (ED) visits and mortality between individuals exposed and not exposed to the flood., Methods: A retrospective cohort study was conducted including 813 724 citizens of Romagna, Italy, from 15 May to 31 August 2023 (ie, 14 weeks after flood inception). The study differentiated between individuals in flood-affected (exposed) and non-affected (unexposed) areas, assessing ED visit rates (overall and by disease category), hospitalisation odds and mortality. Data were analysed using multivariate regression models, adjusting for demographic variables, comorbidities and social frailty, assessed using the Deprivation Index., Results: Of the study population, 586 437 were exposed to the flood, while 227 287 were not exposed. ED visits totalled 33 331 for those exposed to the flood and 13 185 for the unexposed group. Overall, 27 527 (4.7%) of those in the exposed group and 10 829 (4.8%) in the unexposed group experienced at least one ED visit (OR 0.98; 95% CI 0.96 to 1.01). Frequency of access with severe triage scores was higher among those exposed as well as rate of hospitalisation after ED visit. Among those exposed, the rate of ED admission was lower for ophthalmology diseases (OR 0.84; 95% CI 0.77 to 0.92) and general disorders and minor problems (OR 0.85; 95% CI 0.78 to 0.93), and higher for trauma (OR 1.22; 95% CI 1.09 to 1.36) and mental health disorders (OR 1.40; 95% CI 1.17 to 1.75). Exposed individuals had a slightly increased risk of death in the subsequent weeks (OR: 1.09; 95% CI 1.00 to 1.19)., Conclusion: The May 2023 flood in Romagna revealed enhanced vulnerability of the directly affected population, as shown by higher acuity ED presentations and subsequent hospitalisations, as well as more visits for trauma and mental health., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Recent research emphasizes the importance of integrating psychological-emotional factors with nutrition and body composition in athletes. This study investigates the correlations between these aspects in 36 professional rugby players, aiming to identify relationships that could optimize sports performance and overall well-being., Methods: The study sample included 36 male athletes (mean age: 24.4 ± 2.1 years, weight: 86.5 ± 7.1 kg, and height: 181.8 ± 5.7 cm). Four assessment tools were used: the Short Form Health Survey Questionnaire (SF-36) to evaluate quality of life, the Mediterranean diet adherence (MEDI-LITE), the International Physical Activity Questionnaire (IPAQ), and body composition measurements (stadiometer and BIVA). Statistical analyses, including the Shapiro-Wilk test, Pearson, and Spearman correlations, were conducted to explore relationships between the variables., Results: The athletes' mental and physical health was comparable to the general population (mean MCS = 50.5 ± 7.4, PCS = 49.6 ± 9.6). Mediterranean diet adherence was low (mean MEDI-LITE = 8.6 ± 2.6), while physical activity levels were high (mean IPAQ = 2560.5 ± 950.1). Body composition indicated overweight status (mean BMI = 26.15 ± 1.62 kg/m 2 , body fat = 22 ± 4.3%). Positive correlations were observed between mental health, diet adherence, and physical activity, with a stronger link between physical activity and body composition., Conclusions: This study confirms a relationship between psychological-emotional factors, nutrition, and body composition in athletes, suggesting an integrated approach to optimize performance. However, causality remains unconfirmed, and the small sample size limits generalizability. Future research should include larger, more diverse samples to expand these findings.

Cardiac lymphangiomas represent one of the rarest types of cardiac tumors. We describe the case of a 28-year-old male with cystic lymphangioma and hypertrophic cardiomyopathy. There have been only a few cases reported and to the best of our knowledge this is the first documented case associating a cardiac lymphangioma with cardiomyopathy., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Background: The overall risk of long-term adverse events of a transient episode of new-onset atrial fibrillation (AF) in patients with acute coronary syndrome (ACS) remains uncertain. This meta-analysis aimed to assess the prognostic impact of transient new-onset AF complicating ACS., Methods and Results: Cohort studies examining the risk of adverse events in patients with transient new-onset AF compared to those in sinus rhythm after ACS were identified through a comprehensive search of MEDLINE, Scopus, Cochrane, and Google Scholar Library. Studies reporting the incidence of ischaemic stroke events, recurrent AF, or all-cause mortality at the longest follow-up were included. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CI) were synthesized using inverse variance-weighted random-effects meta-analysis. In the seven observational studies included, comprising 151 735 patients, 6 597 (4.3%) experienced transient new-onset AF, which was associated with an increased risk of ischaemic stroke, recurrent AF, or all-cause mortality (HR: 2.24, 95% CI: 1.75-2.85; P < 0.0001; I2 = 30.76%; seven studies). The results remained consistent across each individual endpoint, including ischaemic stroke (HR 2.38, 95% CI: 1.64-3.44; P < 0.01; I2 = 50.2%; five studies), recurrent AF (HR 4.68, 95% CI: 2.07-10.59; P = 0.0002; I2 = 50.2%; four studies), and all-cause mortality (HR 1.36, 95% CI: 1.08-1.71; P = 0.0089; I2 = 53.25%; four studies). Meta-regression analyses revealed a significant increase in these adverse events associated with ST-elevation myocardial infarction (P = 0.001), while there was a tendency for their decrease associated with oral anticoagulant prescription at discharge (P = 0.07)., Conclusions: The occurrence of transient new-onset AF is associated with an elevated long-term risk of stroke, recurrent AF, and all-cause mortality in patients with ACS. Consequently, these data urge randomized clinical trials to assess the best antithrombotic regimen while potentially helping the current treatment decision-making process for these patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Subcellular RNA localization is an underexplored regulatory layer crucial for properly adapting cells to cellular or environmental conditions. Most studies describing RNA localization have been performed by cell fractionation and subsequent RNA quantification from pools of cells, thereby missing information about cell-to-cell variability. RNA single-molecule fluorescent in situ hybridization (smFISH) is an effective technique for detecting single RNA molecules and identifying subcellular accumulation patterns. Nevertheless, obtaining quantitative results from smFISH can be challenging in tissues with high autofluorescence, like in plants. Here, we describe an automated pipeline to detect and quantify nucleocytoplasmic RNA levels from Arabidopsis root smFISH images. This pipeline utilizes free image preprocessing, segmentation, and RNA detection software. The method permits users with any programming skills to analyze batches of images. Suggestions and recommendations for image acquisition, processing, and data analysis are included. This pipeline allows quantitative differences in nucleocytoplasmic distribution at the single-cell level to be studied under different cellular, environmental, and genetic contexts., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Long interspersed nuclear elements 1 (LINE-1) are the most abundant and the only autonomous mobile elements in the human genome. When their epigenetic repression is removed, it can lead to disease, such as autoimmune diseases and cancer. Coeliac disease (CeD) is an immune-mediated disease triggered by an abnormal T-cell response to dietary gluten and a predisposing condition of small bowel adenocarcinoma (SBA), frequently characterized by epigenetic alterations. The aim of this work was to assess LINE-1 methylation by bisulphite pyrosequencing and NanoString® gene transcription analysis in 38 CeD-SBAs compared with 25 SBAs associated with Crohn's disease (CrD-SBAs) and 25 sporadic SBAs (S-SBA). Both analyses were also performed in duodenal mucosae from 12 untreated CeD patients (UCD) and 19 treated CeD patients (TCD), and in 11 samples of normal intestinal mucosa to better investigate the role of LINE-1 deregulation in CeD and in CeD-SBA. A significant loss of LINE-1 methylation was observed in CeD-SBAs and in mucosae from UCD patients (with very similar methylation levels) compared with controls. By contrast, a restoration of normal LINE-1 methylation levels was found in TCD mucosae after a strict gluten-free diet. LINE-1 hypomethylation does not lead to expression of ORF1 and ORF2, with the only exception being for one CeD-SBA. The expression analysis of enzymes modulating DNA methylation and inflammatory genes confirmed that CeD-SBA shared a very similar expression profile of UCD mucosae showing a strong upregulation of genes involved in inflammation, immune response, and T-cell activity compared with TCD mucosae. For the first time, this work demonstrates that loss of DNA methylation is an intrinsic epigenetic feature of CeD, accompanying the immune response as a reversible mechanism in patients following a strict gluten-free diet, and suggests the possible role of LINE-1 hypomethylation in promoting cell adaptability during the gliadin-related inflammatory process. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

Background: With the shift towards personalized medicine, understanding the impact of robotic-assisted total knee arthroplasty (TKA) on patient-reported outcome measures (PROMs) is essential for evaluating its effectiveness and patient satisfaction. The QUAROB (Quality-assessment-of-ROBotic-orthopedic-surgery) study aims at assessing the impact of robotic surgery on quality of care and joint functionality at 6 months post-surgery among patients undergoing robotic-assisted TKA., Methods: This observational, prospective cohort study included patients from Ravenna Hospital, Italy, who underwent elective robotic TKA (2022-2023), and a historical cohort who underwent traditional TKA (2019). PROMs questionnaires (EuropeanQualityofLife-Visual AnalogScale, EQ-VAS, EuropeanQualityofLife-5Dimensions-3Likert, EQ-5D-3L, and KneeinjuryOsteoarthritisOutcomeScore-PatientSatisfaction, KOOS-PS) were administered within 30 days before surgery and 6 months post-surgery. Statistical analysis involved comparing baseline and follow-up PROMs, focusing on patients achieving at least a 10% improvement (Minimal Clinically Important Difference, MCID)., Results: The study enrolled 214 robotic surgery patients, with 208 completing baseline and 103 completing 6-month follow-up questionnaires. Patients undergoing robotic-assisted TKA demonstrated significant improvements in EQ-VAS, EQ-5D-3L, and KOOS-PS scores at 6 months. A significant proportion of patients achieved improvements exceeding the MCID threshold (68.9% for EQ-VAS, 58.3% for EQ-5D-3L, and 68.9% for KOOS-PS). Robotic TKA patients experienced shorter hospital stays (7 vs. 9 days, p < 0.001) and higher engagement in rehabilitation compared to traditional TKA patients., Conclusions: The QUAROB study provides evidence of the impact and benefits of robotic-assisted TKA, highlighting significant enhancements in PROMs, reduced hospital stays, and increased rehabilitation engagement. These outcomes reinforce the role of robotic technology in improving surgical precision and patient satisfaction in orthopedic surgery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Norovirus is associated with 18% of acute gastroenteritis (AGE) cases worldwide. We aim to document the norovirus-related AGE incidence in peri-urban areas of Lima (Peru), evaluating the potential impact of a norovirus vaccine introduction., Methods: A prospective, community-based pediatric cohort study was established at two sites in Lima. Healthy children between 5 and 18 months were contacted weekly for AGE detection during a 6-month period. Stool samples from AGE cases were tested for norovirus by RT-PCR. Incidence and coinfection of norovirus-associated AGE were analyzed. All norovirus-positive samples were genotyped by Sanger DNA sequencing., Results: Among 498 enrolled children, 461 (93%) completed the follow-up period. We detected 799 AGE cases, yielding 676 valid stool samples. Norovirus was detected in 216 samples (32%), with an incidence of 7.7 episodes per 100 child-months (95% CI: 6.7-8.8). Genotypes GII.4 (31%) and GII.6 (22%) were frequent. Campylobacter (43%) and Salmonella spp. (15%) were the most common coinfections with norovirus. Ninety-five percent of study children had received an oral rotavirus vaccine., Conclusion: Norovirus was the second most frequent cause of AGE in this Peruvian cohort with high rotavirus vaccine coverage. An effective norovirus vaccine would have an important public health benefit in this population., Competing Interests: Declarations of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Claudio F. Lanata, Ana I. Gil, Rubelio Cornejo, and Lucie Ecker declare that they received research grant funding to their Institute from Takeda Vaccines Inc. and HilleVax Inc. to conduct this norovirus epidemiology study and to conduct a Phase IIb norovirus vaccine trial. John Weil is an employee of Takeda Pharmaceuticals International AG. Astrid Borkowski is an employee of HilleVax Inc. Giselle Soto and Joan Neyra are employees of the U.S. Government. Ana Goios is an employee of P95 Epidemiology and Pharmacovigilance, which received funding from Takeda Vaccines Inc. and HilleVax Inc. in connection with the conduct of this study. All remaining authors have declared no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: Gastrointestinal medullary carcinoma is a rare histologic subtype of adenocarcinoma. As nonampullary small bowel medullary carcinomas (SB-MCs) are poorly characterized, we aimed to analyse their clinicopathologic and immunohistochemical features and to compare them with nonmedullary small bowel adenocarcinomas (NM-SBAs)., Methods and Results: Surgically resected SBAs collected through the Small Bowel Cancer Italian Consortium were classified as SB-MCs (carcinomas with ≥50% of tumour fulfilling the typical histologic criteria of MC) or NM-SBAs. Immunohistochemistry for cytokeratin (CK)7, CK20, CDX2, programmed death-ligand 1 (PD-L1) and mismatch repair proteins was performed in both SB-MCs and NM-SBAs. SB-MCs were also tested for CK8/18, synaptophysin, SMARCB1, SMARCA2, SMARCA4, and ARID1A and for Epstein-Barr virus (EBV)-encoded RNAs by in-situ hybridization. MLH1 promoter methylation status was evaluated in MLH1-deficient cases. Eleven SB-MCs and 149 NM-SBAs were identified. One (9%) SB-MC was EBV-positive, while 10 (91%) harboured mismatch repair deficiency (dMMR). MLH1 promoter hypermethylation was found in all eight dMMR SB-MCs tested. Switch/sucrose nonfermentable deficiency was seen in two (18%) SB-MCs, both with isolated loss of ARID1A. Compared with NM-SBAs, SB-MCs exhibited an association with coeliac disease (P < 0.001), higher rates of dMMR (P < 0.001), and PD-L1 positivity by both tumour proportion score and combined positive score (P < 0.001 for both), and a lower rate of CK20 expression (P = 0.024). Survival analysis revealed a better prognosis of SB-MC patients compared to NM-SBA cases (P = 0.02)., Conclusion: SB-MCs represent a distinct histologic subtype, with peculiar features compared to NM-SBAs, including association with coeliac disease, dMMR, PD-L1 expression, and better prognosis., (© 2024 The Author(s). Histopathology published by John Wiley & Sons Ltd.)

Hirschsprung disease (HSCR) is the most common congenital motility disorder of the intestine, characterized by the absence of ganglion cells in the myenteric and submucosal plexuses, leading to functional bowel obstruction. Short-segment Hirschsprung disease (SS-HSCR) accounts for the majority of cases, with surgical resection being the cornerstone of treatment. Despite advances in surgical techniques, considerable variability exists in practice regarding the timing of surgery, the choice of technique, and the length of aganglionic rectal cuff to resect. This review synthesizes the current evidence surrounding surgical management of SS-HSCR, discussing technique-specific outcomes and areas for future research, with a focus on optimizing patient care and functional outcomes., Competing Interests: None declared., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Pregnant women are sensitive to the emotions and cues present in social interactions. They may exhibit heightened stress responses when support is lacking in a harmonious environment. The objective of this study was to examine the interaction of family harmony and social support and its association with stress responses among pregnant women. A total of 556 pregnant women were recruited to participate in this study. Psychological stress was measured using the Perceived Stress Scale - 10 (PSS-10). We assessed their perceived levels of family harmony (Family Harmony Scale-5: FHS-5) and social support (Multidimensional Scale of Perceived Social Support; MSPSS). They also provided blood samples for measurement of interleukin-6 (IL-6) as a marker of inflammation. Moderation analysis was conducted with estimation of regression coefficients and 95 % confidence intervals. After adjusting for covariates, the interaction of family harmony and social support in association with IL-6 levels was significant (β = -0.23, p = .045); however, its association with psychological stress was not significant. Specifically, the lack of support within a harmonious family environment was linked to elevated levels of IL-6 in pregnant women (β = 0.26, p = .023). Social interactions lacking supportive gestures have the potential to exacerbate inflammatory responses in pregnant women. Findings underscore the importance of supportive social interactions in promoting the mental well-being of pregnant women., Competing Interests: Declaration of Competing Interest All authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Introduction: and research question: Prognostic factors to predict the behavior of pituitary neuroendocrine tumors (PitNET) are scarce. PD-L1 expression was associated with prognosis in other neuroendocrine neoplasms and we analyzed PD-L1 expression in PitNET, according to the 2022 WHO classification., Material and Methods: A retrospective analysis was performed. Immunohistochemistry was used to define PD-L1 expression, which was quantified as TPS (tumor proportion score). The primary outcome was to assess the correlation between PD-L1 expression and transcription factors (TF), namely T-pit, Pit-1, SF-1 and GATA-3. As secondary outcomes, we evaluated the association between PD-L1 expression and proliferation indexes., Results: Eighty-eight patients were included. The largest group belonged to the SF-1-lineage (48%), followed by tumors of the Pit-1 lineage (32%) and T-pit lineage (17%). PD-L1 expression was associated with Pit-1 expression (p < 0.001) and with the somatotroph, lactotroph and mammosomatotroph subgroups. A TPS ⩾35% showed a 100% sensitivity for the mammosomatotroph subtype, while the optimal cut-off point was 20% for somatotroph and 15% for lactotroph tumors. PD-L1 expression was negatively associated with SF-1 and GATA3 expression(p < 0.001), with an optimal cut-point ≤5%. No association was found between PD-L1 expression and immunohistochemical proliferative factors but PD-L1 expression was associated with female sex and a younger age at diagnosis., Conclusion: PD-L1 expression was associated with PIT-1 lineage, while it was downregulated in SF-1-lineage tumors. No correlation was found with proliferative factors. The role of PD-L1 expression in determining the biological behavior of PitNET remains debated and larger studies are necessary to further confirm these findings., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Giulia Cossu reports financial support was provided by The European Association of Neurosurgical Societies. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objectives: The non-oncological population is relatively under-represented among end-of-life (EOL) patients managed by palliative care (PC) services, and the effects of different PC delivery models are understudied in this population.This retrospective observational study on routinely collected data aimed at evaluating the effects of the extension from workday-only to 24/7 mixed hands-on and advisory home PC service on emergency department (ED) access and emergency medical services (EMS) interventions needed by non-oncological patients during their last 90 days of life, and their probability to die in hospital., Methods: A before-and-after design was adopted comparing preimplementation and postimplementation periods (2018-2019 and 2021-22).We used a difference-in-differences approach to estimate changes in ED access and EMS intervention rates in the postintervention period through binomial negative regression. The oncological population, always exposed to 24/7 PC, was used as a control. A robust Poisson regression model was adopted to investigate the differences regarding hospital mortality. The analyses were adjusted for age, sex and disease grouping by the system involved. Results were reported as incidence rate ratios (IRRs) and ORs., Results: A total of 2831 patients were enrolled in the final analysis.After the implementation of 24/7 home PC, both ED admissions (IRR=0.390, p<0.001) and EMS interventions (IRR=0.413, p<0.001) dropped, as well as the probability to die in hospital (OR=0.321, p<0.001)., Conclusions: The adoption of a 24/7 mixed hands-on and advisory model of home PC could have relevant effects in terms of ED access and EMS use by non-oncological EOL patients under PC., Trial Regisration Number: NCT05640076., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ Group.)

There is a growing interest in the potential use of intracardiac fluid dynamic analysis to better understand cardiac mechanics and identify novel imaging biomarkers of cardiovascular disease. Abnormalities of vortex formation and shape may in fact play a critical role in cardiac function, affecting both efficiency and myocardial workload. Recent advances in imaging technologies have significantly improved our ability to analyze these dynamic flow patterns in vivo, offering new insights into both normal and pathological cardiac conditions. This review will provide a comprehensive overview of the available imaging techniques for intracardiac fluid dynamics analysis, highlighting their strengths and limitations. By synthesizing the current knowledge in this evolving field, the paper aims to underscore the importance of advanced fluid dynamic analysis in contemporary cardiology and to identify future directions for research and clinical practice., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: High-sensitivity cardiac troponin (hs-cTn) is a key biomarker for myocardial injury, yet its prognostic value in intensive cardiovascular care units (ICCU) remains poorly understood. We aimed to assess the association between peak hs-cTn levels and prognosis in ICCU patients., Methods: All patients admitted to a tertiary care center ICCU between July 2019 - July 2023 were prospectively enrolled. Patients were divided into five groups according to their peak hs-cTnI levels: A) hs-cTnI <100 ng/L; B) hs-cTnI of 100-1000 ng/L; C) hs-cTnI of 1000-10,000 ng/L; D) hs-cTnI of 10,000-100,000 ng/L and E) hs-cTnI ≥100,000 ng/L. The primary outcome was all-cause mortality at one year., Results: A total of 4149 patients (1273 females [30.7 %]) with a median age of 69 (IQR 58-79) were included. Group E was highly specific for myocardial infarction (97.4 %) and especially for ST segment elevation myocardial infarction (STEMI) (87.5 %). Patients in group E were 56 % more likely to die at 1-year in an adjusted Cox model (95 % CI 1.09-2.23, p = 0.014) as compared with group A. Subgroup analyses revealed that among STEMI patients, higher peak hs-cTnI levels were not associated with higher mortality rate (HR 1.04, 95 % CI 0.4-2.72, p = 0.9), in contrast to patients with NSTEMI (HR 7.62, 95 % CI 1.97-29.6, p = 0.003)., Conclusions: Peak hs-cTnI levels ≥100,000 ng/L were linked to higher one-year mortality, largely indicative of large myocardial infarctions. Notably, the association between elevated hs-cTnI levels and mortality differed between STEMI and NSTEMI patients, warranting further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Vascular calcification (VC) is a biological phenomenon characterized by an accumulation of calcium and phosphate deposits within the walls of blood vessels causing the loss of elasticity of the arterial walls. VC plays a crucial role in the incidence and progression of chronic kidney disease (CKD), leading to a significant increase in cardiovascular mortality in these patients. Different conditions such as age, sex, dyslipidemia, diabetes, and hypertension are the main risk factors in patients affected by chronic kidney disease. However, VC may occur earlier and faster in these patients if it is associated with new or non-traditional risk factors such as oxidative stress, anemia, and inflammation. In chronic kidney disease, several pathophysiological processes contribute to vascular calcifications, including osteochondrogenic differentiation of vascular cells, hyperphosphatemia and hypercalcemia, and the loss of specific vascular calcification inhibitors including pyrophosphate, fetuin-A, osteoprotegerin, and matrix GLA protein. In this review we discuss the main traditional and non-traditional risk factors that can promote VC in patients with kidney disease. In addition, we provide an overview of the main pathogenetic mechanisms responsible for VC that may be crucial to identify new prevention strategies and possible new therapeutic approaches to reduce cardiovascular risk in patients with kidney disease.

Background: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are recommended for reducing the renal and cardiovascular risk in patients with chronic kidney disease (CKD) based on the positive results reported by clinical trials. However, real-world data on the efficacy and the safety of these drugs in CKD population followed in nephrology setting are lacking., Methods: We report the effects of dapagliflozin in CKD patients by using data collected during a learning program in which 105 nephrologists added dapagliflozin (10 mg/day) to consecutive patients referred to their renal clinics. Efficacy endpoints were the albuminuria change and the determinants of an albuminuria decline ≥30%. Adverse events were also collected., Results: A total of 1724 patients with CKD (age 67.4 ± 13.2 years, 72.8% males, diabetes 59.9%, eGFR 43.5 ± 17.4 ml/min/1.73 m 2 , severe albuminuria 70.1%) received dapagliflozin for 4 ± 1 months. Dapagliflozin significantly reduced body weight (-1.3 kg), eGFR (-0.27 ml/min/month), and blood pressure (-3.6/-1.7 mmHg). Albuminuria declined by 25.1% (95%CI 23.0-27.2) from 500 mg/day [IQR 225-1425] to 320 mg/day [IQR 100-900]. Albuminuria reduction was ≥30% in 48.3% of patients, 0-29% in 37.6% while it increased in 14.1% of patients. At logistic regression analysis, older age, female sex, use of mineralocorticoid receptor antagonist, higher eGFR, and higher albuminuria were all significant predictors of albuminuria decline ≥30%. We collected 46 side effects leading to drug discontinuation in 36 patients (2%), with acute kidney injury and urinary tract infection being the most frequent adverse events., Conclusions: We provide evidence of the anti-proteinuric efficacy of short-term dapagliflozin in the presence of good safety profile in patients with CKD followed in nephrology., Competing Interests: R.M. has been member of Advisory Boards for Amgen, Astellas, Bayer, and GSK, and has received fees for lectures from Amgen, Astellas, Bayer, and Vifor Pharma. F.A. has been member of Advisory Boards for Vifor and Sanofi, and has received fees for lectures from AstraZeneca and Amgen. V.B. fees for lectures from Astra Zeneca. Y.B. has received fees for scientific consultation and/or lectures by AstraZeneca and Vifor Pharma. V.M. has received fees for lectures or scientific consultation from Takeda, CSL Behring, BioCryst, Pharming, GSK, Astellas, Astra Zeneca, Bayer, Alexion, CSL Vifor, and Kiowa Kyrin. D.M. has received fees for lectures by Fresenius Medical Care and AstraZeneca. L.D.N. has received fees for scientific consultation and/or lectures by Astellas, AstraZeneca, Mundibiopharma, and Vifor Pharma. A.A., L.A., S.B., L.B., V.C., G.C., P.C., P.F., C.G., E.I., S.L.R., M.M., M.N., F.N., C.P., D.S., R.S., F.S., and T.T. declare no financial interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Drug delivery to the brain is challenging due to the restrict permeability of the blood brain barrier (BBB). Recent studies indicate that BBB permeability increases over time during physiological aging likely due to factors (including extracellular vesicles (EVs)) that exist in the bloodstream. Therefore, inspiration can be taken from aging to develop new strategies for the transient opening of the BBB for drug delivery to the brain., Results: Here, we evaluated the impact of small EVs (sEVs) enriched with microRNAs (miRNAs) overexpressed during aging, with the capacity to interfere transiently with the BBB. Initially, we investigated whether the miRNAs were overexpressed in sEVs collected from plasma of aged individuals. Next, we evaluated the opening properties of the miRNA-enriched sEVs in a static or dynamic (under flow) human in vitro BBB model. Our results showed that miR-383-3p-enriched sEVs significantly increased BBB permeability in a reversible manner by decreasing the expression of claudin 5, an important tight junction protein of brain endothelial cells (BECs) of the BBB, mediated in part by the knockdown of activating transcription factor 4 (ATF4)., Conclusions: Our findings suggest that engineered sEVs have potential as a strategy for the temporary BBB opening, making it easier for drugs to reach the brain when injected into the bloodstream., Competing Interests: Declarations. Ethics approval and consent to participate: The collection of umbilical cord blood (UCB) was approved by the ethical committee of Dr. Daniel de Matos Maternity Hospital in Coimbra (protocol HUC-01-11), Portugal. The collection of adult blood was approved by the Faculty of Medicine of the University of Coimbra and the Portuguese Institute for Blood and Transplantation (IPST) in the facilities of Blood and Transplantation Center of Coimbra (CSTC) (protocol: CE-088/2020). All the donors of the UCB and adult blood signed an informed consent form, in compliance with the Portuguese legislation. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Coronary artery disease (CAD) is a main cause of morbidity and mortality. The effectiveness of coronary revascularization in chronic coronary syndromes (CCS) is still debated. Our recent study showed the superiority of coronary revascularization over optimal medical therapy (OMT) in reducing cardiovascular (CV) mortality and myocardial infarction (MI). The recent publication of the ORBITA-2 trial suggested superiority of percutaneous coronary revascularization (PCI) in reducing angina and improving quality of life. Therefore, we aimed to provide an updated meta-analysis evaluating the impact of PCI on both clinical outcomes and angina in CCS., Methods: Relevant studies were screened in PubMed/Medline until 08/01/2024. Randomized controlled trials (RCTs) comparing PCI to OMT in CCS were selected. The primary outcome was CV death. Secondary outcomes were MI, all-cause mortality, stroke, major bleeding and angina severity., Results: Nineteen RCTs involving 8616 patients were included. Median follow-up duration was 3.3 years. Revascularization significantly reduced CV death (4.2% vs. 5.5%; OR = .77; 95% CI .62-.96, p = .02). Subgroup analyses favoured revascularization in patients without chronic total occlusions (CTOs) (p = .052) and those aged <65 years (p = .02). Finally, a follow-up duration beyond 3 years showed increased benefit of coronary revascularization (p = .04). Secondary outcomes analyses showed no significant differences, except for a lower angina severity in the revascularization group according to the Seattle Angina Questionnaire (SAQ) (p = .04) and to the Canadian Cardiovascular Society (CCS) classification (p = .005)., Conclusions: PCI compared to OMT significantly reduces CV mortality and angina severity, improving quality of life in CCS patients. This benefit was larger without CTOs, in patients aged <65 years and with follow-up duration beyond 3 years., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Aspiration following anesthesia is a major patient issue and a difficulty for anesthesiologists. Aspiration syndromes are more common than anticipated, and the condition is frequently undetected. Clinical signs are often dictated by the characteristics of aspiration, such as the infectivity of the material, its volume, and the severity of the underlying clinical condition. Pulmonary aspiration can cause an acute or persistent inflammatory response in the lungs and upper airways that can be complicated by tracheobronchitis, aspiration pneumonia, aspiration pneumonitis, acute respiratory distress syndrome, and subsequent bacterial infection due to particle, acid, and bacteria-related processes. Aspiration during anesthesia, while relatively rare, poses significant risks for patient morbidity and mortality. Chemical and bacterial aspiration provide distinct diagnostic and management issues. Preventive strategies such as a complete preoperative risk assessment, adherence to fasting rules, proper patient positioning, and the use of protective airway devices are critical in reducing aspiration risk. In addition, drugs such as proton pump inhibitors can help lower stomach acidity and volume. Innovations in monitoring techniques, better training, and awareness activities are critical to enhancing aspiration event management. Given the importance of this entity, this narrative review sought to make an updated overview of the management of aspiration after anesthesia: chemical versus bacterial, differential diagnosis, management, and prevention., Competing Interests: None declared., (Thieme. All rights reserved.)

Pneumoperitoneum, which is established for laparoscopic surgery, has systemic implications on the renal system and may contribute to acute kidney injury or postoperative renal dysfunction. Specifically, when the pressure exceeds 10 mmHg, pneumoperitoneum decreases renal blood flow, leading to renal dysfunction and temporary oliguria. The renal effects of pneumoperitoneum stem from both the direct effects of increased intra-abdominal pressure and indirect factors such as carbon dioxide absorption, neuroendocrine influences, and tissue damage resulting from oxidative stress. While pneumoperitoneum can exacerbate renal dysfunction in patients with pre-existing kidney issues, preserving the function of the remaining kidney is crucial in certain procedures such as laparoscopic live donor nephrectomy. However, available evidence on the effects of pneumoperitoneum on renal function is limited and of moderate quality. This review focuses on exploring the pathophysiological hypotheses underlying kidney damage, mechanisms leading to oliguria and kidney damage, and fluid management strategies for surgical patients during pneumoperitoneum.

Limited research has been conducted to examine the factors during early childhood that may contribute to conduct problems in later stages of life. This study aimed to investigate the relationship between family and school environments during early childhood and conduct problems in adolescence. In Wave 1 (W1), the study recruited 502 participants, aged 5-6 years, from Hong Kong local kindergartens, with 51.4% boys. One of their parents provided information about family socioeconomic status (SES), parent-child recreational activities, and child screen time, whereas the class teacher rated their school readiness using the Chinese version of the Early Development Instrument. Data on the number of special facilities were obtained from the kindergartens. In Wave 2 (W2), the same parents of 395 participants were asked about their involvement in their children's education. Finally, in Wave 3 (W3), the parents of 206 participants completed the Conduct Problem scale of the Strength and Difficulties Questionnaire to evaluate the level of conduct problems in the participants. The results of the path analysis revealed that higher W1 family SES was associated with fewer W3 conduct problems through an increase in W1 and W2 parental involvement in children's learning and play activities. Findings have implications for understanding the impact of early-life family and school environments on adolescent conduct problems. Early childhood interventions that promote family resources and positive parent-child interactions have the potential to reduce adolescent conduct problems., (© 2024 The Author(s). Family Process published by Wiley Periodicals LLC on behalf of Family Process Institute.)

In serous borderline ovarian tumor (SBOT), a micropapillary (MP) pattern has been considered analogous to intraepithelial low-grade serous carcinoma (LGSC). On this account, it is reasonable to hypothesize that MP-SBOT is more likely to be associated with extraovarian LGSC localizations (also referred to as 'invasive implants') compared to conventional SBOT. The aim of this study was to investigate the potential association between a MP pattern and invasive implants in SBOT. Three electronic databases were searched from 2000 (year of publication of histological criteria for MP-SBOT) to 2023 for all studies assessing the presence of invasive implants in conventional SBOT vs MP-SBOT. Exclusion criteria were sample size <20, overlapping patient data, reviews. The association between MP pattern and invasive implants was assessed by using odds ratio (OR), with a significant p-value<0.05. Seven studies with 1766 SBOT were included, out of which 205 (11.5 %) were MP-SBOT, 462 (26 %) had implants and 62 (3.5 %) had invasive implants. A MP pattern was significantly associated with the presence of invasive implants (OR=7.33, 95 % CI 3.61-14.86) (p<0.001), with low heterogeneity among studies (I 2 =28 %). In conclusion, a MP pattern in SBOT is significantly associated with extraovarian LGSC localization, supporting that it represents intraepithelial LGSC., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nothing for declaration If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions. There are several key rationales based on physicochemical principles and clinical considerations that justify the application and investigation of such therapies as evidenced by multiple ex vivo, experimental and clinical observations. Accordingly, unspecific adsorptive extracorporeal therapies have now been applied to the treatment of a wide array of conditions from poisoning to drug overdoses, to inflammatory states and sepsis, and acute or chronic liver and kidney failure. In response to the rapidly expanding knowledge base and increased clinical evidence, we convened an Acute Disease Quality Initiative consensus conference dedicated to such treatment. The data show that hemoadsorption has clinically acceptable short-term biocompatibility and safety, technical feasibility and experimental demonstration of specified target molecule removal. Pilot studies demonstrate potentially beneficial effects on physiology and larger studies of endotoxin-based hemoadsorption have identified possible target phenotypes for larger randomized controlled trials. Moreover, in a variety of endogenous and exogenous intoxications, removal of target molecules has been confirmed in vivo. However, some studies have raised concerns about harm, or failed to deliver benefits. Thus, despite many achievements, modern hemoadsorption remains a novel and experimental intervention with limited data, and a large research agenda., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Photoaging induced by ultraviolet A (UVA) radiation is mainly caused by the reactive oxygen species (ROS) increase, which trigger undesirable changes in the skin, such as inflammatory reactions, wrinkles, hyperpigmentation, and loss of elasticity. In this context, plant ingredients have been highlighted in recent decades due to their antioxidant mechanisms. This study investigated the potential of Hypericum brasiliense ethanolic extract against UVA-induced damage in 3T3 fibroblasts. Cells exposed to a single UVA dose (4 J/cm 2 , 30 min) were treated with different extract concentrations. The results showed that H. brasiliense extract has antioxidant potential, mitigating UVA-induced stress by reducing ROS and lipid peroxidation. Furthermore, the extract stimulated fibroblast proliferation, suggesting its potential to restore cell viability after radiation-induced damage. The search for replacing synthetic actives with natural ones reinforces the importance of these findings on the antioxidant and regenerative properties of H. brasiliense extract, making it a promising anti-aging ingredient or a sunscreen adjuvant.

Study Design: Retrospective analysis., Objective: The aim of this study is to evaluate the functional outcomes and the health-related quality of life (HRQOL) in patients undergoing en bloc resection of spinal tumor., Summary of Background Data: En bloc resection in the spine is a surgical procedure designed to completely remove a tumor in one piece, with wide margins preserved, in order to reduce the risk of local recurrences. This demanding procedure has been shown to improve local control and survival rate, besides a relatively high morbidity., Methods: Between 2016 and 2021, 70 patients underwent en bloc resection surgery for a primary spine tumor and 38 came out to be eligible for this analysis. Eligibility criteria include at least one follow-up visit within a two-year period from surgery and Patient Reported Outcomes evaluation collected prospectively at baseline and at least one follow- up in the range 4-24 months. The outcome variables (EQ5D Numeric Scale and Index, SF36 scores and NRS score) were analyzed with multilevel linear mixed-effects regression. Baseline- (age, gender, localization, histotype, number of levels of resection, previous surgery) and time-dependent covariates (adverse events, spinal cord damage) were included., Results: Beside a slight improvement of all the scores, no significant differences were found between baseline and follow up times for EQ-5D-3L Numeric Scale and Index and for SF-36 Standardized Physical component. SF-36 Standardized Mental component appeared to be significantly better at 12-month FU compared to baseline. Ultimately, age over 50 years old and the occurrence of adverse events emerged to be as the two main factor determining worsening in several HRQOL scores. Pain came out to be significantly reduce at 24-month compared to baseline., Conclusions: The aim of en bloc resection in the treatment of primary spinal tumors is to improve survival rates and reduce local recurrences. Despite its radicality, our preliminary results suggest that patients experience a slight to moderate improvement postoperatively compared to their preoperative perceived health status., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Noli, Alcherigi, Griffoni, Pesce, Rosa, Evangelisti, Pipola, Davassi, Monetta, Barbanti Brodano, Terzi, Ghermandi, Tedesco, Girolami, Bandiera and Gasbarrini.)

Purpose: Falls are a major concern for people with Parkinson's disease (PwPD) due to associated motor and non-motor impairments. Promoting safe mobility behaviour may be an effective fall prevention intervention, however this concept is poorly articulated in the literature. The aim of this scoping review was to map out the definition and concepts of safe mobility behaviour to draw implications for PwPD., Materials and Methods: The Joanna Briggs Institute methodology for scoping reviews was followed. Studies involving older adults (aged ≥ 65 years) and/or PwPD that sought to define, describe, and/or explain this concept were included., Results: Of the 21,936 records retrieved, 124 publications were included. No studies defined safe mobility behaviour. However, its performance was described as a combination of observable actions and cognitive processes. Mobility behaviour was influenced by an interaction between the person, environment, and task performance., Conclusion: We propose a definition for safer mobility behaviour as any protective action and associated functional cognitive process used to reduce the likelihood of a fall during mobility-related activities. It is unique to each person and occurs across a continuum of safer to riskier behaviour. Future research developing and testing interventions targeting safer mobility behaviour for PwPD is warranted.

Facial expression perception is influenced by body posture, with perception biased toward the body emotion. Previous research has suggested that the magnitude of this biasing influence of body posture is driven by individual differences in the precision of facial expression representations underlying discrimination abilities, where lower precision leads to a greater influence of body posture. It is unclear however whether similar mechanisms might drive the influence of contextual cues in Autism, which is often characterised by reduced facial expression discrimination abilities. Here, we addressed this question by using online psychophysical methods to determine the precision of isolated face and body expression representations of anger and disgust, and the influence of body on facial expression perception, in autistic and non-autistic adults. Both groups showed a strong influence of body context on facial expression perception, but this influence was larger in the autistic group, mirroring their lower overall precision of facial expression representations relative to non-autistic individuals. Crucially, the magnitude of the biasing influence of body posture in both groups was related to the precision of individuals' facial expression representations. The results suggest that similar principles govern the integration of facial expression and body posture information in both autistic and non-autistic individuals., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Growing evidence indicates an association between disordered eating and a range of mental health problems, including anxiety, depression and emotional dysregulation., Aims: This study aimed to explore whether reducing risk factors for eating disorders, such as body dissatisfaction and low self-esteem, through school-based programmes can enhance adolescent mental health., Method: We searched PubMed, PsycINFO, EMBASE and Web of Science from the date of inception to 15 October 2023. Data were synthesised by using a systematic narrative synthesis framework, and formal assessments were conducted to assess the quality of the included studies., Results: After title/abstract screening and full-text assessment, 13 articles met the pre-specified inclusion criteria, comprising a total of 14 studies ( n = 5853). Notably, three studies encompassed multiple programmes, leading to the identification of 17 eating disorder prevention programmes. Among these programmes, seven (41%) employed dissonance-based approaches. Topics covered in the programmes included psychoeducation, body acceptance, sociocultural issues, nutrition and physical activities, self-esteem and stress coping. Ten (59%) of the programmes were effective in improving adolescent mental health. Six of the 14 studies (43%) did not specify follow-up time, and quality assessments found the majority to be of either high (five studies, 36%) or fair (eight studies, 57%) quality., Conclusions: The findings from the ten effective programmes consistently support the use of body acceptance strategies in improving the mental health of adolescent students. Brief interventions delivered by trained, non-licensed facilitators appear good for the sustainable implementation of in-school psychological services to support well-being among adolescents.

Modern advances in systemic and localized therapies for patients with renal cell carcinoma (RCC) have significantly improved patients' outcomes. If disease progression occurs after initial treatment, clinicians often have multiple options for a first salvage therapy. Because salvage and initial treatments both may affect overall survival time, and they may interact in unanticipated ways, there is a growing need to determine sequences of initial therapy and first salvage therapy that maximize overall survival while maintaining quality of life. The complexity of this problem grows if a second salvage therapy must be chosen for patients with treatment-resistant disease or a second progression occurs following first salvage. On November 9, 2023, a think tank was convened during the International Kidney Cancer Symposium (IKCS) North America to discuss challenges in accounting for postprogression therapies when estimating overall survival (OS) time based on randomized controlled trial (RCT) data. The present manuscript summarizes the topics discussed, with the aim to encourage adoption of statistical methods that account for salvage therapy effects to obtain scientifically valid OS estimation. We highlight limitations of traditional methods for estimating OS that account for initial treatments while ignoring salvage therapy effects and discuss advantages of applying more sophisticated statistical methods for estimation and trial design. These include identifying multistage treatment strategies, correcting for confounding due to salvage therapy effects, and conducting Sequentially Multiple Assignment Randomized Trials (SMARTs) to obtain unbiased comparisons between multistage strategies. We emphasize the critical role of patient input in trial design, and the potential for information technology (IT) advances to support complex trial designs and real-time data analyses. By addressing these challenges, future RCTs can better inform clinical decision-making and improve patient outcomes in RCC., Competing Interests: Declaration of competing interest Pavlos Msaouel reports honoraria for scientific advisory board membership for Mirati Therapeutics, Bristol Myers Squibb, and Exelixis; consulting fees from Axiom Healthcare; nonbranded educational programs supported by Exelixis, Pfizer, and DAVA Oncology; leadership or fiduciary roles as a Medical Steering Committee member for the Kidney Cancer Association and a Kidney Cancer Scientific Advisory Board member for KCCure; and research funding from Takeda, Bristol Myers Squibb, Mirati Therapeutics, Regeneron Pharmaceuticals, and Gateway for Cancer Research. Eric A. Singer reports honoraria for data safety monitoring board membership for Aura Biosciences and leadership or fiduciary roles as a Medical Steering Committee member for the Kidney Cancer Association. Kathryn E Beckermann received funding to the institution for preclinical awards including BMS-IASLC-LCFA, Pionyr, Arsenal Bio, and Aravive, as well as funds as a consultant to Aravive, Aveo, Arcus, Alpine Bioscience, BMS, Exelixis, Merck, Eisai, Nimbus, and Adicet. Bradley A. McGregor reports consulting fees from Arcus, BMS, Daiichi, Eisai, Exelixis, Gilead, Lily, Pfizer as well as research funding to institution from BMS, Exelixis, Gilead, and Pfizer. Ulka N. Vaishampayan reports consulting fees from BMS. Novartis, Merck, Exelixis, Pfizer, Glilead and Alkermes, as well as speaker fees from Bayes and Exelixis. Eric Jonasch reports research support from Abbvie, Arrowhead, Aveo, BMS, Corvus, Merck, NiKang, ProFoundBio, Telix, honoraria from Aveo, Clinical Care Options, DAVA, EBSCO, Eisai, Exelixis, GSK, IDEO Oncology, i3 Health, Ipsen, Kaplan, Merck, Novartis, NiKang, Petra Drugstore, Plexus, leadership position in NCCN Guidelines (Vice-Chair Kidney Cancer Panel), member of the NCI RCC Steering Committee, and board Member of the International Kidney Cancer Coalition. Katie Coleman is employed by the Rare Cancer Research Foundation and has received honoraria from Exelixis for a speaking engagement related to patient advocacy. Nizar M. Tannir reported receiving and personal fees (honoraria) from Calithera Biosciences during the conduct of the study; and grants (sponsored trial) from Calithera Biosciences, Bristol Myers Squibb (BMS), Nektar Therapeutics, Arrowhead Pharmaceuticals, and Novartis, as well as personal fees (honoraria) from Calithera Biosciences, BMS, Eisai Medical Research, Merck Sharp & Dohme (MSD), Deka Biosciences, Neoleukin Therapeutics, Exelixis, and Ono Pharmaceutical outside the submitted work. Daniel M Geynisman reports honoraria from Targeted Oncology, consulting fees from Pfizer, Exelixis, AstraZeneca, Seattle Genetics/Astellas, Merck, and Bristol-Myers Squibb, as well as research funding to institution from Merck, Astellas Pharma, Harpoon Therapeutics, Arvinas, and CG Oncology. Walter M. Stadler reports consulting fees for participation in Data and Safety Monitoring Board from Astra-Zeneca, Merck, Pfizer, and Treadwell Therapeutics, other consulting fees from Astra-Zeneca, Aveo, Caremark/CVS, EMA Wellness, Fortress Biotech, and Xencor, speakers bureau for CME programs from Dava Oncology, Global Academyc for Medical Education, OncLive, PeerView, Research to Practice, and Vindico, research funding to institution from Abbvie, Amgen, Astra-Zeneca, Astellas (Medivation), Bayer, Bristol-Myers-Squibb, Boehringer-Ingelheim, Calithera, Corvus, Eisai, Exilixis, Genentech (Roche), Johnson & Johnson (Janssen), Merck, Novartis, Pfizer, Seattle Genetics, X4Pharmaceuticals, Xencor, stock holdings from Fortress Biotech, Expert Witness for Sandoz, as well as miscellaneous fees from Cancer (ACS), Up-To-Date, and the Kidney Cancer Journal. Yousef Zakharia reports advisory board / consulting fees from Bristol Myers Squibb, Amgen, Janssen, Eisai, Exelixis, Genzyme Corporation, Pfizer, EMD Serono, Astellas, and Seagen, Grant/research institutional support from Pfizer, Exelixis, and Eisai, as well as honoraria for data safety monitoring board membership from Janssen Research and Development. Daniel D. Shapiro has no disclosures., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)